The present invention is generally in the area of methods and devices for producing vascular tissue grafts from living vascular tissue, and particularly for making autologous grafts.
Vascular grafts are commonly used by surgeons to bypass obstructions to blood flow caused by the presence of atherosclerotic plaques. Vascular grafts also are used in other applications such as providing arterial-venous shunts in dialysis patients, vascular repair or replacement and treating aneurysms. Grafts for bypass are often, but not exclusively, used in the coronary arteries, the arteries that supply blood to the heart.
The materials used to construct a vascular graft usually are either synthetic or of biological origin, but combinations of synthetic and biological materials are under development. The most widely used biological vascular grafts are autologous saphenous vein or mammary artery. Some common synthetic grafts are made of polytetrafluoroethylene (PTFE) (e.g., GORTEX™) or polyester (e.g., DACRON™). Autologous grafts have generally been used more successfully than synthetic grafts. Autologous grafts remain patent (functional) much longer than synthetic grafts, and saphenous veins often fail in less than five years. The short lifetime of synthetic grafts is especially evident with small diameter (less than 7 mm diameter) grafts, as most small diameter synthetic grafts occlude within one to two years or less.
Small diameter vascular grafts are particularly used in coronary artery bypass surgery. Internal mammary artery (IMA) is the autologous graft of choice, because it typically has a longer life than venous grafts (95% patent at five years versus 85% patent at two years). Mammary arterial tissue, however, is difficult to harvest, is typically not available in lengths sufficient for multiple bypasses, and its removal can result in problems such as problematic wound healing. Moreover, obtaining sufficient venous tissue for repairing an occluded artery can be problematic in patients with venous conditions such as varicose veins and especially in second or third surgeries in the same patient. Literature also suggests that IMA used in bypass procedures either fails soon after transplantation or remains patent indefinitely. See, e.g., Bergsma, et al., Circulation 97(24):2402-05 (1998); Cooley, Circulation 97(24):2384-85 (1998).
Other arteries such as the gastroepipolic, gastric, radial, and splenic also are used in coronary bypass procedures. In some cases, autologous or homologous saphenous vein preserved by freezing or other processes is used. A recent American Heart Association/American College of Cardiology consensus document strongly recommends a move to total arterial revascularization (Eagle, et al. “ACC/AHA Guidelines for coronary artery bypass graft surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines”, Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery, American College of Cardiology/American Heart Association, J. Am. Coll. Cardiol., 34(4):1262-347 (1999)).
Development of a longer lasting small-diameter vascular graft is the subject of much academic and industrial research. One current approach is to combine cell culture and biomaterials technologies to make a living, “tissue engineered” graft. This effort, however, is hindered by the requirements of a successful graft. The graft should be self-repairing, non-immunogenic, non-toxic, and non-thrombogenic; should have a compliance comparable to the artery being repaired; should be easily sutured by a surgeon; and should not require any special techniques or handling procedures. Grafts having these characteristics are difficult to achieve. Despite the substantial effort to date and the potential for significant financial reward, academic and industrial investigators have failed to produce graft materials that have demonstrated efficacy in human testing.
Efforts to avoid or minimize the need for vascular grafts for repair of otherwise healthy vascular tissue have been described. For example, Ruiz-Razura et al., J. Reconstructive Microsurgery, 10(6):367-73 (1994) and Stark et al., Plastic & Reconstructive Surgery, 80(4):570-78 (1987) disclose the use of a round microvascular tissue expander for acute arterial elongation to examine the effects on the tissue of such acute hyperextension. The expander is a silicone balloon that is placed under the vessel to be elongated. The balloon is filled with saline over a very short period, causing acute stretching and elongation of the vessel. The method is purported to be effective for closure of arterial defects up to 30 mm without the need for a vein graft. These techniques are appropriate for trauma, but are not used for restoring blood flow in vessels that are occluded, for example by disease, which are treated by surgically bypassing the obstruction with a graft. The disclosed methods and devices fail to provide an autologous graft or versatile substitute. Moreover, the acute stretching may damage the vessel.
It has been demonstrated, however, that axial stretching can increase smooth muscle cell proliferation in an intact blood vessel, thereby substantially enhancing blood vessel growth. See Conklin, “Viability of Porcine Common Carotid Arteries in a Novel Organ Culture System” MS Thesis, Georgia Institute of Technology, 1997); Han, et al., “Axial Stretch Increases Cell Proliferation in Arteries in Organ Culture”, Advances in Bioengineering ASME, BED 48:63-64 (2000).
PCT WO 99/60952 to Georgia Tech Research Corporation and U.S. Pat. No. 6,322,553 to Vito describe devices and methods for producing axial growth by mechanically stimulating a blood vessel using axial distention. These devices anchor to exterior surfaces of the blood vessels, and consequently their use in vivo is necessarily invasive, at least requiring endoscopic surgery. The size of the devices also may limit the sites that are suitable for implantation. It would be advantageous to develop devices and methods that are less invasive and more easily installed and used in vivo. It would also be tremendously beneficial to the patient to be able to eliminate the need for surgery before removal of the grown blood vessel for use as an autologous graft. It would be desirable to provide minimally- or non-invasive devices and methods for stretching and growing blood vessels in vivo. It also would be desirable to provide simple devices and methods for creating natural blood vessel suitable for grafting, and for making an autologous blood vessel graft with fewer surgeries.